Intrathecal Cytarabine, Methotrexate, and Hydrocortisone for the Prevention of High-Grade Chimeric Antigen Receptor T-Cell-Associated Neurotoxicity Syndrome

NCT06895473 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: STUDY00028106NCI-2025-00937
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well cytarabine (Ara-C), methotrexate, and hydrocortisone given between the spinal cord and the membranes that protect it (intrathecal \[IT\]) works in preventing high-grade immune effector-associated neurotoxicity syndrome (ICANS) in patients receiving chimeric antigen receptor (CAR) T-cell therapy. ICANS is a challenging complication of CAR T-cell therapy that causes neurological effects varying from mild headaches or temporary confusion to hallucinations, swelling in the brain, and seizures. Between 20%-70% of patients receiving CAR T-cell therapy show symptoms of neurotoxicity.

Conditions

Hematopoietic and Lymphatic System Neoplasm

Outcome Measures

Primary Outcomes (1)

• Incidence of American Society for Transplantation and Cellular Therapy (ASTCT) ≥ grade 3 immune-effector cell associated neurotoxicity syndrome (ICANS)

  Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.

  From first dose of intrathecal (IT) chemotherapy (chimeric antigen receptor [CAR]-T day 4) to CAR-T day 30

Secondary Outcomes (4)

• Incidence of ASTCT any grade ICANS

  From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30

• Incidence of lumbar puncture/IT treatment related adverse events (AEs) and serious adverse events (SAEs)

  From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30

• Mean (range) cumulative dose of corticosteroid use

  From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30

• Incidence of anakinra use

  From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30

Study Arms (1)

Supportive Care (cytarabine, methotrexate, hydrocortisone)

EXPERIMENTAL

Patients receive cytarabine IT, methotrexate IT, and hydrocortisone IT over 3-5 minutes via LP on day 4 post-SOC CAR T-cell therapy in the absence of unacceptable toxicity or development of ICANS. Patients who do not develop ICANS of any grade, also receive hydrocortisone IT on day 7 post SOC CAR T-cell therapy. Additionally, patients undergo CSF sample collection throughout the study.

Procedure: Biospecimen Collection; Drug: Cytarabine; Procedure: Lumbar Puncture; Drug: Methotrexate; Drug: Therapeutic Hydrocortisone

Interventions

Biospecimen Collection PROCEDURE

Undergo CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Supportive Care (cytarabine, methotrexate, hydrocortisone)

Cytarabine DRUG

Given IT

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Supportive Care (cytarabine, methotrexate, hydrocortisone)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Supportive Care (cytarabine, methotrexate, hydrocortisone)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Supportive Care (cytarabine, methotrexate, hydrocortisone)

Therapeutic Hydrocortisone DRUG

Given IT

Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, Hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid

Supportive Care (cytarabine, methotrexate, hydrocortisone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent. Participant or legally authorized representative (LAR) must provide written informed consent prior to any study-specific procedures or interventions
• Age ≥ 18 years. All genders, races, and ethnic groups will be included
• Must be receiving SOC Yescarta® or Tecartus® in the inpatient setting
• Agree to adhere to institutional guidelines for contraception during the first 30 days post CAR-T
• Rationale for eligibility criteria based on contraception and pregnancy (both participants and partners of a sperm-producing participant): It shall be known to all participants that the effects of CAR-T or IT chemotherapy on the developing human fetus are unknown. For this reason, persons of reproductive potential must agree to use adequate contraception. Should a participant or participant's sexual partner become pregnant or suspect a pregnancy while participating in this study, the individual should inform their treating physician immediately
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Platelet count \> 50,000/mm\^3 (μL)
• Adequate coagulation tests including international normalized ratio (INR) \< 1.6 and fibrinogen \> 100

You may not qualify if:

• Active/concurrent diagnosis of any central nervous system (CNS) hematologic malignancy
• History or presence of CNS disorder such as poorly controlled seizure disorder (seizure within the 12 months), transverse myelitis, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• Known history of hypersensitivity to IT chemotherapy
• Subject has a contraindication to LP including:
• Presence of a posterior fossa mass
• Skin infection near puncture site
• Uncorrected bleeding diathesis
• Suspicion of increased intracranial pressure
• Acute spinal cord trauma
• Subject is receiving an antiplatelet and/or anticoagulant that cannot be held prior to LP according to best available evidence
• Known bleeding disorders
• Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or would put the participant at risk

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• American Society of Clinical Oncology: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Cytarabine; Spinal Puncture; Methotrexate; merphos; Hydrocortisone

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Stephen E Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: March 26, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (1)